Systemic injection of the DAD1 antagonist SCH 23390 reduces saccharin seeking in rats.
Systemic injection of the DAD1 antagonist SCH 23390 reduces saccharin seeking in rats.
复制标题
DOI：
10.1016/j.appet.2016.05.008
复制
发表时间：
2016-10-01
期刊：
影响因子：
5.4
通讯作者：
Grimm JW
中科院分区：
文献类型：
--
作者：
Aoyama K;Barnes J;Koerber J;Glueck E;Dorsey K;Eaton L;Grimm JW
条件性线索可以引发药物和蔗糖寻求行为，这些行为已被证明依赖于多巴胺（DA）D1受体。如果DAD 1受体也参与一般的寻求行为，那么阻断这些受体应该会减少对无热量、无药物滥用的药物如糖精的寻求行为。雄性Long-Evans大鼠46只，每天用0.3%糖精溶液压杆1h，连续10 d。杠杆反应也激活了一个音调加上一个白色刺激光。该复合刺激持续5秒。强制戒断1天后，在消退试验前15分钟，大鼠接受SCH 23390全身注射（0、1或10 μg/kg IP;每组n=15-16）。经10 μg/kg SCH 23390预处理后，主动杠杆反应显著减少，主动视杆反应次数显著减少，提示音+光提示的主动视杆反应次数显著减少，证明全身性SCH 23390可减少糖精寻求。在该组中，整个测试阶段的反应斜率也显著更陡，表明SCH 23390可能降低了糖精寻找的持续性。结果表明，DAD 1受体参与糖精寻求，并将先前证明的DAD 1拮抗剂的抗寻求作用推广到无热量、无药物滥用的抑制剂。
Conditioned cues can elicit drug- and sucrose-seeking behaviors that have been shown to depend on dopamine (DA) D1 receptors. If DAD1 receptors are also involved in seeking behavior in general, blocking these receptors should reduce seeking behavior for a non-caloric, non-drug of abuse reinforcer such as saccharin. Forty-six male Long-Evans rats lever pressed for 0.3% saccharin solution 1 h/day for 10 days. A lever response also activated a tone plus a white stimulus light. This compound stimulus lasted for 5 seconds. After 1 day of forced abstinence, rats received systemic (0, 1, or 10 μg/kg IP; n=15–16 per group) injections of SCH 23390 15 minutes prior to extinction testing. Systemic SCH 23390 reduced saccharin seeking evidenced by a significant reduction in active lever responding and a significant reduction in the number of active lever-contingent deliveries of the tone+light cue following pretreatment with 10 μg/kg SCH 23390. The slope of responding across the Test session in this group was also significantly steeper, indicating that SCH 23390 may have reduced the persistence of saccharin seeking. The results indicate that DAD1 receptors are involved in saccharin seeking and generalize the previously demonstrated anti-seeking effects of DAD1 antagonism to a non-caloric, non-drug of abuse reinforcer.